Thursday, 3 June 2010

Chillies for arthritis

If you’ve ever been complacent in the kitchen when chopping chillies, you’ll know just how irritating they can be to the more sensitive parts of the body. In centuries past, herbs with such obvious effects on the body were frequently experimented with as therapeutics, and various healing powers were imposed upon them. The 17th century herbalist Culpepper attributed many virtues to these pungent fruit, such as supposed effects on digestion and the kidneys. However, the crude extracts of chillies that appear in the British Pharmacopoeia of the late 19th century were intended mainly for external use. Modern medicine is still exploring the potential uses of the fiery chemical that chillies contain.

Many are probably familiar with capsaicin as the principle active constituent of chilli peppers, since it is employed by the police as an irritant to incapacitate violent offenders. Once concentrated capsaicin contacts the mucosal surfaces of the eyes, nose and throat, the pain is absolutely excruciating (I inadvertently got some up my nose once in the lab, and it was an amazing experience that I choose not to repeat). If you sprayed a similar solution of capsaicin on your hands and rub it in, the pain would be much less severe, possibly just a mild tingling sensation (since skin is an effective barrier), depending on the strength of the preparation. This tingling, burning sensation is still exploited in some over-the-counter pharmacy preparations (which come with warnings about avoiding getting it in your nose and eyes.) These are hangers on from the days when such preparations would have been used as counter-irritants. Capsaicin isn’t unique, though, and many similarly burning or irritating materials were similarly employed.

A popular and long-lasting counter-irritant concoction appears in the Parke, Davis & Co. catalogues from early last century (mine is the 1921 edition). Their “Capsolin” ointment contained not only crude capsaicin but a mixture of similarly irritating herbal extracts:

Oleoresin of capsicum
Oil of turpentine
Oil of cajuput
Oil of croton

All of these can be classed roughly as rubefacients: chemicals that cause reddening of the skin. Contemporary accounts of this potion suggest that it was very painful to apply, although this would depend, of course, on how much was applied to a given surface area of skin. Capsolin was initially indicated for use where ever a counter-irritant was required, i.e. in any disease in which an inflammatory reaction was held to be responsible for the symptoms (many diseases of the day). It probably had little actual therapeutic effect in diseases beyond being a distracting placebo. It would have felt invigorating on arthritic knees on a cold morning, and our modern experiences in this setting can tell us something about how effective it might have been (see below). Somewhere along the way Capsolin (and other rubefacients) fell into use by sporty types, who used it as a means to “warm” muscles. Capsolin was not alone – the less irritating oil of wintergreen is still used for this counter-irritant purpose by athletes.

A quick Google search reveals that Capsolin was popular with American baseball players, acquiring the moniker 'atomic balm'. Some players seem to have used heroic amounts of it – entire tubes during the course of a single game. Much as one becomes accustomed to the heat of chillies as a culinary additive, these players must have deadened their nerves to some extent. It is this additional effect of regular, heavy use of potent preparations that brings us to the modern interest in capsaicin.

We classify the different sensory nerves in the body according to the modalities they respond to (eg. heat, cold, pressure, stretch), how fast they conduct nervous impulses to the central nervous system, and what neurotransmitters they release. When you stub your toe, the first impulses to reach the brain are conducted by nerves that carry impulses very quickly. This initial sharp pain triggers the gut feeling of “Oh, this is going to hurt”, and a second or so later, impulses carried by slower nerve fibres reach the brain; these nerves are responsible for the longer-lasting, dull and throbbing pain. Anyone with children will recognise the slight lag in the arrival of these impulses via different nerve fibres, since the wrong parental reaction (distraction) between them is the difference between “oops” and several minutes of screaming. Capsaicin acts on these slower sensory nerves. When applied for hours at low concentrations, capsaicin will deplete these sensory nerves of their neurotransmitters so that any impulses carried by them cannot be communicated to the central nervous system. At the same time, the pain induced elicits endorphin production in the brain. This combination of deadening peripheral nerves, as well as the release of endogenous pain-killers in the central nervous system produces effects much like true analgesia. Prolonged use (weeks), or short term use of very high concentrations (much higher than those in Capsolin) may eventually lead to damage to sensory nerves, producing a longer term relief from pain at the site of application. This is probably the effect that baseballers achieved: they became insensitive to the dull, throbbing pain from their worn out pitching shoulders. Few doctors would have recommended it over a proper rest, but professional athletes at the time could rarely afford to miss a game.

Once it became clear just how capsaicin acts on the body, and how specifically it desensitises or destroys subtypes of sensory nerves, there was renewed interest in it as a therapeutic. Capsaicin was touted as a potential treatment for chronically painful conditions such as osteoarthritis and neuropathic pain (pain arising from disease-addled nerve fibres), with the aim of desensitising or damaging sensory nerves. We can gain an insight into how effective counter-irritation might have been by considering the results of modern, controlled trials of capsaicin in these conditions. Regularly applied low doses of capsaicin cream or patches does not appear to be consistently effective in relieving the pain of osteoarthritis, and these doses are high enough that some patients are put off by the burning heat. With continued application, some desensitisation occurs, but it is unclear whether this produces a clinically significant reduction in pain. Indeed, such low dose creams have been used as placebos in trials of stronger formulations. Where capsaicin appears to be useful is in neuropathic pain, where high dose applications have been shown to reduce pain indices. These doses probably approximate those used historically by baseball players, and are so painful that they can only be applied after the relevant area has been treated with a local anaesthetic. Such is the damage to sensory nerves after such an application that the degree of pain relief lasts for weeks. Whether patients with milder, arthritic pain will prefer such a treatment to conventional pain-killers remains to be seen. Nevertheless, lower dose formulations are still considered third-line agents for those that find it provides some relief, whether it is effective, or just an old-fashioned, counter-irritant placebo.

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